High MET gene copy number predicted poor prognosis in primary intestinal diffuse large B-cell lymphoma.

Feb 2013

Huang WT, Chuang SS.

Abstract

BACKGROUND: MET is a proto-oncogene with its copy number (CN) alterations been reported in some cancers, but not in primary intestinal diffuse large B-cell lymphoma (PI-DLBL) yet.

METHODS:

In this retrospective study, we performed histology and chart reviews, immunohistochemistry and quantitative polymerase chain reaction for MET CN alterations on 28 surgically resected PI-DLBLs.

RESULTS:

There were 12 men and 16 women with a median age of 70 and a mean follow-up of 32 months. The median MET CN was 2.20 (range, 1.04 to 3.35). CN gain was observed in 11 cases, including 5 with CN greater than 3. Nine patients (32%) had diploid CN and eight (29%) with CN loss. Patients with gain or diploid CN showed significantly worse prognosis (P = 0.046) than those with CN loss. Furthermore, MET CN greater than 3 was associated with an adverse outcome (P = 0.003). Intestinal perforation at presentation was the sole clinicopathological factor associated with a poor prognosis (P = 0.004) and perforation was correlated with CN greater than 3 (P = 0.002).

CONCLUSIONS:

Our finding of MET CN gain as a poor prognostic factor in PI-DLBL patients might serve as the rationale for targeting MET signaling pathway in the treatment of these patients. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1637072378895873.

Diagnostic Pathology

Lenalidomide in diffuse large B-cell lymphoma.

2012

Thieblemont C, Delfau-Larue MH, Coiffier B.

Source

Hematology and Oncology Department, Hôpital Saint-Louis, AP-HP and IUH, INSERM U728, University Paris VII, 75010 Paris, France.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma (NHL) in adults. Even if the natural history of DLBCL has been improved with the advent of immunochemotherapy, the survival results obtained with current treatment options clearly indicate that new agents or novel approaches are needed. Lenalidomide (Revlimid, Celgene Corporation, Summit, NJ, USA), an analogue of thalidomide, is an immunomodulatory drug with pleiotropic mechanisms of action potentially adding to immunochemotherapy. We present here the biological rational for the use of lenalidomide in DLBCL in light of recent advances in the pathophysiology of the disease and the therapeutic results of the most recent trials published in literature or reported in meetings in relapsed/refractory situations as well as in first-line treatment.

PubMed

Long-term remission of primary bone marrow diffuse large B-cell lymphoma treated with high-dose chemotherapy rescued by in vivo rituximab-purged autologous stem cells.

2012

Kazama H, Teramura M, Yoshinaga K, Masuda A, Motoji T.

Source

Department of Hematology, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

Abstract

Primary bone marrow diffuse large B-cell lymphoma (DLBCL) is a rare type of extranodal lymphoma with poor prognosis. Here, we report a case of primary bone marrow DLBCL successfully treated with high-dose chemotherapy and rescued by in vivo rituximab-purged autologous stem cells. A 39-year-old woman visited our hospital because of anemia. Bone marrow examination revealed a large B-cell lymphoma invasion. An (18)F-fluorodeoxyglucose positron emission tomography scan revealed disseminated bone marrow uptake without evidence of dissemination at other sites. These findings led to a diagnosis of primary bone marrow DLBCL. Our patient underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy and achieved complete remission. Subsequently, she received high-dose chemotherapy with an in vivo rituximab-purged autologous stem cell transplant. Seven years have passed since the transplantation, and she remains in remission. This suggests that transplantation of an in vivo rituximab-purged autograft is a promising strategy for primary bone marrow DLBCL.

Case Reports in Medicine

Rituximab Maintenance Therapy After Autologous Stem-Cell Transplantation in Patients With Relapsed CD20+ Diffuse Large B-Cell Lymphoma: Final Analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma.

Oct 2012

Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N,Shpilberg O, Dührsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Brière J, Salles G, Moskowitz CH, Glass B.

Source

Christian Gisselbrecht and Josette Brière, Hôpital Saint Louis, Paris; Nicolas Mounier, Centre Hospitalier Universitaire de l'Archet, Nice; Noel J. Milpied, Hôpital Haut-Lévêque, Pessac; Gilles Salles, Hospices Civils de Lyon and Université de Lyon, Lyon, France; Norbert Schmitz and Bertram Glass, Asklepios Klinik St Georg, Hamburg; Ulrich Dührsen, Universitätsklinikum Essen, Essen; Andreas Viardot, Universitätsklinik Ulm, Ulm, Germany; Devinder Singh Gill, Princess Alexandra Hospital, Woodville, South Australia; David D. Ma, St Vincent's Hospital Sydney, Darlinghurst, New South Wales; Ray Lowenthal, Royal Hobart Hospital, Tasmania, Australia; David C. Linch, University College London, Cancer Institute, London; John Radford, University of Manchester, Christie Hospital National Health Service Trust, Manchester, United Kingdom; Marek Trneny, Charles University General Hospital, Prague, Czech Republic; Andre Bosly, Université Catholique de Louvain Mont-Godinne, Yvoir, Belgium; Nicolas Ketterer, Clinique Bois-Cerf, Lausanne, Switzerland; Ofer Shpilberg, Davidoff Center, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Hans Hagberg, Akademiska Sjukhuset, Uppsala, Sweden; and Craig H. Moskowitz, Memorial Sloan-Kettering Cancer Center, New York, NY.

Abstract

PURPOSE

The standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT). The impact of maintenance rituximab after ASCT is not known. 

PATIENTS AND METHODS

In total, 477 patients with CD20(+) DLBCL who were in their first relapse or refractory to initial therapy were randomly assigned to one of two salvage regimens. After three cycles of salvage chemotherapy, the responding patients received high-dose chemotherapy followed by ASCT. Then, 242 patients were randomly assigned to either rituximab every 2 months for 1 year or observation. 

RESULTS: 

46% v 56% for relapsed disease after 12 months), secondary age-adjusted International Prognostic Index (saaIPI) more than 1 - EFS: 37% v 61% for saaIPI , - and prior treatment with rituximab - EFS: 47% v 59% for no prior rituximab - . A significant difference in EFS between women at sixty three percent and men at forty six percent was also observed in the rituximab group. In the Cox model for maintenance, the saaIPI was a significant prognostic factor , as was male sex. 

CONCLUSION

In relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT.

Full Text: Journal of Clinical Oncology

Epstein Barr virus presence in pediatric diffuse large B-cell lymphoma reveals a particular association and latency patterns. Analysis of viral role in tumor microenvironment.

Sept 2012

Cohen M, De Matteo E, Narbaitz M, Carreño FA, Preciado MV, Chabay PA.

Source

Molecular Biology laboratory. Pathology Division. Ricardo Gutiérrez Children's Hospital. Buenos Aires, Argentina. melucohen@ffyb.uba.ar.

Abstract

Non-Hodgkin's lymphoma represents 6-10% of pediatric malignancies, and diffuse large B-cell lymphoma (DLBCL) is one of the 3 major subtypes. The 2008 WHO classification included a new entity, Epstein-Barr virus (EBV)-positive DLBCL of the elderly, affecting patients >50 years. It has been demonstrated that EBV may play a role in tumor microenvironment composition, disturbing anti-tumor immune response and disease progression.

Since most studies were performed in adults, our aim was to assess EBV presence and latency pattern, as well as T-cell microenvironment in a pediatric DLBCL series of Argentina. The study was conducted on formalin-fixed paraffin-embedded biopsies from 25 DLBCL patients. EBERs expression was performed by in situ hybridization, while EBV gene expression was analyzed using real-time PCR. LMP1, LMP2A, CD3, CD4, CD8 and Foxp3 expression were assessed by immunohistochemistry (IHC). Forty percent of cases showed EBV expression, with a significantly higher incidence among patients <10 years (p=0.018), and with immunosuppressed (p=0.023). T-cell subsets were not altered by EBV presence. 

Full EBV latency antigen expression (latency type III) was the most frequently pattern observed, together with BZLF1 lytic gene expression. One patient showed II like pattern (LMP1 without LMP2A expression). Based exclusively on IHC, some patients showed latency II/III (EBERs and LMP1 expression) or I (EBERs only). These findings suggest that EBV association in our series was higher than the previously demonstrated for elderly DLBCL and that EBV latency pattern could be more complex from those previously observed. Therefore, EBV could be an important cofactor in pediatric DLBCL lymphomagenesis.

PubMed

Isolated mononeuropathy multiplex-a rare manifestation of intravascular large B-cell lymphoma.

Sept 2012

Lynch KM, Katz JD, Weinberg DH, Lin DI, Folkerth RD.

Source

*Department of Neurology, St Elizabeth's Medical Center, Boston, MA †Department of Neuropathology, Brigham and Women's Hospital, Boston, MA.

Abstract

ABSTRACT: Intravascular large B-cell lymphoma, also known as angiotrophic large cell lymphoma, is a rare disorder where neoplastic lymphoid cells proliferate within the walls of small- to medium-sized blood vessels. Peripheral neuropathy and other neurological manifestations, including stroke and dementia, are common, but cases of isolated multiple mononeuropathies in the absence of systemic symptoms are distinctly rare. We present an unusual case of biopsy-proved angiotrophic large cell lymphoma presenting exclusively with multiple mononeuropathies.

PubMed